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Research Funding:

TSW is supported by a career development grant by the Department of Veterans Affairs (CDA1-002-09F). This study does not have any specific funding, and the Department of Veteran Affairs had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The Heritability of Amyotrophic Lateral Sclerosis in a Clinically Ascertained United States Research Registry

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Journal Title:

PLoS ONE

Volume:

Volume 6, Number 11

Publisher:

, Pages e27985-e27985

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Article | Final Publisher PDF

Abstract:

Background The genetic basis of amyotrophic lateral sclerosis (ALS) is not entirely clear. While there are families with rare highly penetrant mutations in Cu/Zn superoxide dismutase 1 and several other genes that cause apparent Mendelian inheritance of the disease, most ALS occurs in families without another affected individual. However, twin studies suggest that all ALS has a substantial genetic basis. Herein, we estimate the genetic contribution to ALS in a clinically ascertained case series from the United States. Methodology/Principal Findings We used the database of the Emory ALS Center to ascertain individuals with ALS along with their family histories to determine the concordance among parents and offspring for the disease. We found that concordance for all parent–offspring pairs was low (<2%). With this concordance we found that ALS heritability, or the proportion of the disease explained by genetic factors, is between 40 and 45% for all likely estimates of ALS lifetime prevalence. Conclusions/Significance We found the lifetime risk of ALS is 1.1% in first-degree relatives of those with ALS. Environmental and genetic factors appear nearly equally important for the development of ALS.

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Wingo et al. have dedicated the work to the public domain by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.

This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (http://creativecommons.org/publicdomain/zero/1.0/).

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